A research done by Cindi Morshead, a professor in the Donnelly Centre for Cellular and Biomolecular Research, and led by her team put forward that a drug called Metformin which is used to treat diabetes can also help in the repairmen of brain functions and its logical and analytical capabilities. But this is conditional to the presence or absence of estradiol, a sex hormone; which is only found in females.
Authors : Maham Imran and Sundus Babur
This study was published on September 11, 2019, and it all started when Freda Miller and her team started treatment for childhood brain injuries in a hospital in Toronto. During this research, it was discovered that the drug metformin was highly capable to treat or develop and improve brain repairs and motor functions in children. To confirm this hypothesis, Metformin was tested on newborn mice to check its affect whenever mice had a stroke.
Brain controls the cognitive, logical and intellectual abilities of the body. If there is a brain injury, it could result in the loss of a lot of cognitive abilities and can lead to many other problems, which is why the researchers’ team wanted to know if the drug metformin would give rise to the said cognitive recovery.
Metformin (Metformin hydrochloride) is a type of medicine known as a Biguanide. They are crystalline compounds with basic properties. Its function is linked to an improved peripheral sensitivity to insulin. This takes place by lowering the amount of sugar in the blood of diabetic patients. Metformin does this by lowering the amount of sugar produced in the liver, and also increasing the sensitivity of muscle cells to insulin. It was further being tested for activating stem cells in the brain, which can self-renew and give rise to different types of brain cells to replace those killed by injury.
Professor Morshead first wanted to see if the drug was even relevant to proper and improved brain functioning. This is why this trial was conducted; to see how much effect Metformin has, when it comes to cognitive abilities. Her student Rebecca Rudy initiated stroke in mice and then regularly provided them with the drug metformin, then they were daily tested to see if the cognitive abilities had improved or not. After many days when the tests were checked, it was found that the drug was working on the mice and was even giving recovery to them; but something unexpected had occurred.
The drug only gave results on the adult female mice; the male mice had no improvement whatsoever. This showed that the neural stem cells of adult female were activated by Metformin and it did not affect any of the male mice.
The reason behind this was that the performance of metformin was enhanced due to estradiol, the female sex hormones. While on the other hand, the male sex hormone; testosterone inhibits the effect of metformin which results in no change in the mice’s abilities to recover cognitive brain damage. This was confirmed when the adult female mice’s ovaries were removed and the drug was tested once again. The results were different this time and they were similar to that of the male mice. It showed no recovery in the adult female mice as well.
Estradiol, also spelled oestradiol, is a major female sex hormone. In actuality, it is the estrogen steroid hormone and it is involved in the regulation of the menstrual cycle, estrous cycle and the reproductive cycles in female. Estradiol is responsible for the development of female secondary sexual characteristics such as the widening of the hips, breast and a female-associated pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the uterus, and vagina during puberty, adulthood, and pregnancy as well as the maintenance of mammary glands. It also has important effects in many other tissues including the brain, bone, fat, skin and liver.
It was also confirmed that the process of the drug only worked on a specific sex and age of that sex. This research was conducted when male animal research was more predominant. The reason behind this was that the female brain contains more and complicated hormones as compared to the males. It is easier to interpret information receives from males as it is not as complicated as females. Since the female hormones causes a lot of problems when advancing in science and it is considered as a setback when starting any research; that is why male subjects or animals are used more in comparison to female subjects.
As the same researches are used to study the entire human race, the sex bias is believed to have failed the clinical trials which were used in making general rules for both genders. This led to the misdiagnosis and inappropriate therapies for women, as highlighted in a recent article in Science.
The purpose of this ongoing research was to see the repurposing of the drug metformin in brain repairs. Although this research was done on a small basis, it is still not confirmed if it would actually have affect in humans. This was conducted by a team of collaborators Dr. Donald Mabbott and Dr Bouffet who are Head of Neurosciences and Mental Health Programs and Directors of Brain Tumor Programs for children with brain injuries, and this was all led by Cindi Morsheads.
This research further proves that although male and females may share many of their functions, but the line is drawn when hormones are added to the mix. Yes female body shows a lot of fluctuation in the data collected due to their hormonal imbalance, but that certainly does not mean that no research should be done on female subjects. In fact, female subject just might be what the new researchers need right now; as the female body may provide gthwn with information and relations that men never could.
The research was supported by the funding from the Canadian Institutes of Health Research, which in 2016 mandated its grant holders to account for sex dependent differences in animal research, as well as from the Ontario Institute for Regenerative Medicine, Medicine by Design, Brain Canada, the Stem Cell Network and the Ontario Brain Institute.